JP2013128872A - Gel producing apparatus, medical gel, and method for producing gel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a gel producing apparatus capable of producing gel connected in series.SOLUTION: The gel producing apparatus includes a fluid jetting part for jetting a first fluid; a flow part for allowing a second fluid to flow in a predetermined direction; and a control part for controlling the operation of the fluid jetting part. The control part jets the first fluid into the second flowing fluid to produce first gel, and jets the first fluid into the second flowing fluid so as to contact a part of the first gel in the second fluid, thereby producing second gel and producing gel connected in series of the first gel and second gel.

Description

  The present invention relates to a gel manufacturing apparatus, a medical gel, and a gel manufacturing method.

  There is known a method for producing a gel by a droplet discharge method in which a liquid (gel material) serving as a gel material is discharged toward a gelling material that gels the liquid. For example, a discharge port (nozzle) that discharges the gel material at a certain interval is arranged for the gelled material in a stationary state. And the method and apparatus which manufactures the gel by making the droplet of the gel material discharged from a nozzle by the droplet discharge method react with the gel material of a stationary state are disclosed (for example, refer patent document 1). ).

JP 2001-232178 A

  According to the method of Patent Document 1, a gel having a desired size can be generated by adjusting the discharge amount of droplets. In particular, micro-sized microcapsules and the like can be generated.

  In recent years, it is expected to be applied to the medical field and the food field by appropriately selecting a liquid (gel material) as a raw material for generating such a gel. Under such circumstances, it is considered to use a plurality of gels in a string (fiber form). For example, it is considered to use a thread-like gel as a thread used for suturing during surgery or a biomaterial such as nerve tissue. However, in the conventional gel manufacturing method, it is difficult to generate gels in a state of being connected in series (filamentous gels) even though individual gels can be generated individually.

  An object of the present invention is to provide a gel manufacturing apparatus capable of generating a gel in a state of being connected in series.

  A main invention for achieving the above object includes a fluid ejecting unit that ejects a first fluid, a flow unit that causes a second fluid to flow in a predetermined direction, and a control unit that controls the operation of the fluid ejecting unit. The control unit is configured to generate the first gel by injecting the first fluid into the flowing second fluid, and the first fluid in the second fluid. The first fluid is ejected into the flowing second fluid so as to be in contact with a part of the first gel to form a second gel, and the first gel and the second gel It is the gel manufacturing apparatus characterized by producing | generating the gel of the state which continued in series.

  Other features of the present invention will become apparent from the description of the present specification and the accompanying drawings.

It is a conceptual diagram of the filamentous gel formed. It is the schematic of the gel manufacturing apparatus 1. 2 is a cross-sectional view illustrating the structure of the ejection head 11. FIG. It is a figure explaining the outline | summary of gel production | generation operation | movement in order of a time series. 5A to 5C are diagrams for explaining the relationship between the interval P between adjacent droplets and the diameter d of the droplets. It is explanatory drawing of a sodium alginate. It is explanatory drawing which shows the intermediate | middle aspect which changes from sodium alginate to a calcium alginate gel. It is explanatory drawing of a calcium alginate gel. It is the schematic of the gel manufacturing apparatus 1 in the modification of 1st Embodiment. It is the schematic of the gel manufacturing apparatus 2. FIG. It is a figure which shows the example of the filamentous gel produced | generated by 3rd Embodiment.

  At least the following matters will become clear from the description of the present specification and the accompanying drawings.

A gel manufacturing apparatus comprising: a fluid ejecting unit that ejects a first fluid; a flow unit that causes a second fluid to flow in a predetermined direction; and a control unit that controls the operation of the fluid ejecting unit, The controller generates the first gel by injecting the first fluid into the flowing second fluid, and contacts the part of the first gel in the second fluid. The first fluid is injected into the flowing second fluid to generate a second gel, and the first gel and the second gel are connected in series to generate a gel. The gel manufacturing apparatus characterized by the above-mentioned.
According to such a gel manufacturing apparatus, a filamentous (fibrous) gel in a state of being connected in series can be generated with high accuracy.

In this gel manufacturing apparatus, the frequency when the first fluid is intermittently ejected from the fluid ejecting unit is f, the diameter of the gel formed by the first fluid is d, and the second It is desirable to satisfy the relationship of v / f ≦ d, where v is the fluid flow velocity.
According to such a gel manufacturing apparatus, when a plurality of gels are generated, two gels that are continuously formed are easily adjacent to and in contact with each other. Adjacent gels are successively bonded to each other, so that a filamentous gel having a shape in which a plurality of gels are connected in series is easily generated.

In such a gel manufacturing apparatus, it is preferable that the fluidizing portion is caused to flow so as to have a portion in which the flow direction of the second fluid is a linear direction.
According to such a gel manufacturing apparatus, the flow rate of the second fluid can be easily kept constant, and the filamentous gel can be generated stably. Moreover, if the flow direction of the second fluid is a linear direction, it is easy to suppress the generated filamentous gel from being tangled while flowing in the second fluid.

In such a gel manufacturing apparatus, it is desirable that the fluidizing portion rotate and flow the second fluid in a spiral shape.
According to such a gel manufacturing apparatus, the amount of the second fluid necessary for generating the gel is reduced, and the gel manufacturing cost can be saved. Further, since the gel manufacturing apparatus can be configured compactly, space saving can be achieved.

In this gel manufacturing apparatus, the first fluid is an aqueous solution containing polysaccharides or proteins, the second fluid is an aqueous solution containing a polyvalent metal salt, and the first fluid is the second fluid. It is desirable to form a gel by a curing reaction in contact with the fluid.
According to such a gel manufacturing apparatus, it is possible to generate a filamentous gel that is harmless to the human body and has high applicability to the medical field. Moreover, since it is possible to form a shell made of a hydrophilic gel, it is possible to generate a filamentous gel that has high water retention performance and that can easily adjust osmotic pressure with the external environment.

In this gel manufacturing apparatus, the first fluid is a liquid that gels when cooled, the second fluid is a liquid that cools the first fluid, and the first fluid It is desirable to produce a gel by producing a gel by cooling a fluid in contact with the second fluid.
According to such a gel manufacturing apparatus, it is possible to manufacture a gel whose hardness can be freely adjusted by adjusting the cooling temperature. In addition, since water can be used as the second fluid, the cost of the material can be kept low.

In this gel manufacturing apparatus, the first fluid is a liquid that gels by an enzyme reaction, the second fluid is an aqueous solution containing an enzyme, and the first fluid is the second fluid. It is desirable to produce a gel by contacting it with a fluid to produce the gel by an enzymatic reaction.
According to such a gel manufacturing apparatus, it can adjust based on the hardness of the filamentous gel produced | generated by adjusting the density | concentration of the 1st fluid and the density | concentration of the enzyme contained in a 2nd fluid. In addition, it can be applied to various fields such as medical care and biotechnology.

Moreover, the medical gel manufactured with this gel manufacturing apparatus becomes clear.
According to such a medical gel, since a filamentous gel whose length and thickness can be freely adjusted can be manufactured, it can be used as a surgical thread or biological tissue.

  A step of injecting the first fluid into the second fluid flowing in a predetermined direction to generate the first gel; and contacting a part of the first gel in the second fluid. And the step of injecting the first fluid into the flowing second fluid to form a second gel, wherein the first gel and the second gel are connected in series. A gel production method that produces a gel in a fresh state is revealed.

=== First Embodiment ===
<About gel>
In the present embodiment, a fluid droplet is formed by ejecting a first fluid that is a raw material of the gel, the fluid droplet is brought into contact with the second fluid, and a part or the whole of the fluid droplet is hardened (cured). ) To form a gel. In this case, since the fluid droplet is formed in a substantially spherical shape, the generated gel also has a shape close to a sphere. In addition, it is also possible to produce | generate the gel which has the structure of a "capsule" by hardening a part of fluid droplet formed with a 1st fluid with a 2nd fluid.

  In the following embodiments, the first fluid and the second fluid are both assumed to be liquids. Specific details of the first fluid and the second fluid will be described later.

  In the present embodiment, a plurality of substantially spherical gels (capsules) are connected in series to form a gel in the form of a “string” (fibrous) (hereinafter also referred to as a thread gel). FIG. 1 shows a conceptual diagram of a filamentous gel formed in this embodiment. As shown in the figure, adjacent gels are joined together at a portion indicated by hatching to be connected like a chain, and a thread-like gel is generated.

<Configuration of gel production apparatus>
In the first embodiment, a filamentous gel is generated using the gel manufacturing apparatus 1 that ejects the first fluid to the second fluid while flowing the second fluid in a predetermined direction (for example, a linear direction). To do. In FIG. 2, the schematic of the gel manufacturing apparatus 1 is shown. The gel manufacturing apparatus includes a fluid ejecting unit 10, a fluidizing unit 20, and a control unit 50.

  For the sake of explanation, as shown in FIG. 2, a coordinate axis composed of an X axis, a Y axis, and a Z axis is set. The Z axis is a vertical direction (a downward direction in FIG. 2), the X axis is a direction perpendicular to the Z axis, and the Y axis is a direction perpendicular to the Z axis and the X axis.

(Liquid injection unit 10)
The liquid ejecting unit 10 ejects the first fluid to form droplets. The liquid ejecting unit 10 includes an ejecting head 11 and a first fluid tank 12.

  The ejection head 11 ejects the first fluid by a predetermined amount to form droplets of the first fluid. In the present embodiment, the first fluid is basically ejected in the Z-axis direction (vertically downward direction). However, the ejection head 11 can eject the first fluid in a direction inclined with respect to the Z-axis direction.

  FIG. 3 is a cross-sectional view for explaining the structure of the ejection head 11. In this embodiment, the ejection head 11 includes a nozzle 111, a piezo element PZT, a fluid supply path 112, a nozzle communication path 114 (corresponding to a volume chamber), and an elastic plate 116 (corresponding to a diaphragm).

  The first fluid stored in the first fluid tank 12 is supplied to the nozzle communication path 114 via the fluid supply path 112. A voltage signal having a plurality of pulses generated by the control unit is applied as a drive signal to the piezoelectric element PZT which is a piezoelectric element. When a drive signal is applied, the piezo element PZT expands and contracts in accordance with the drive signal, causing the elastic plate 116 to vibrate. Then, the volume of the nozzle communication path 114 is changed, and the first fluid supplied into the nozzle communication path 114 is moved so as to correspond to the amplitude of the drive signal.

  The movement of the first fluid will be specifically described. The piezo element PZT of the present embodiment has a characteristic of contracting in the vertical direction in FIG. 3 when a voltage is applied. When a voltage larger than a certain voltage is applied as a drive signal, the piezo element PZT contracts in the vertical direction in FIG. 3 and deforms the elastic plate 116 in a direction to increase the volume of the nozzle communication path 114. At this time, the fluid surface in the nozzle 111 moves in the direction of the inside of the nozzle 111 (upper side in FIG. 3). Conversely, when a smaller voltage is applied from a certain voltage, the piezo element PZT extends in the vertical direction in FIG. 3 and deforms the elastic plate 116 in a direction to reduce the volume of the nozzle communication path 114. At this time, the fluid surface of the nozzle 111 moves in the direction of the outside of the nozzle 111 (the lower side in FIG. 3). As described above, when the volume of the nozzle communication path 114 is changed, the pressure in the nozzle communication path 114 varies, and the first fluid filled in the nozzle communication path 114 can be ejected from the nozzle 111. The ejected first fluid (liquid) becomes spherical (droplet) due to its surface tension. That is, by changing the amplitude (voltage magnitude) of the drive signal applied to the piezo element PZT, the size (amount of fluid) of the ejected droplet can be adjusted. Thereby, a gel of a desired size can be formed accurately. Moreover, the ejection cycle of the first fluid can be adjusted by changing the frequency of the drive signal applied to the piezo element PZT.

  If oxygen molecules are dissolved in the first fluid, bubbles are generated in the nozzle communication path 114 during the pressure fluctuation. Therefore, it is desirable that dissolved air (oxygen) be removed in advance from the first fluid used in the present embodiment.

  Although details will be described later, in this embodiment, it is required to accurately adjust the diameter d of the droplet and the ejection frequency f of the first fluid in order to generate a thread-like gel. If it is a piezoelectric element (piezo element) as described above, it becomes easy to freely control the ejection amount and ejection timing of the fluid by adjusting the voltage waveform of the drive signal.

  The first fluid tank 12 is a tank that stores a first fluid that is a raw material of the gel, and supplies the first fluid to the ejection head 11 via a fluid transmission path (not shown).

(Fluid part 20)
The flow unit 20 causes the second fluid to continuously flow in a predetermined direction, thereby generating a river-like flow. In the present embodiment, the flow unit 20 is assumed to flow the second fluid along the X-axis direction. The flow unit 20 includes a flow passage 21, a second fluid tank 22, and a flow mechanism 23.

  The flow passage 21 is a groove-shaped device extending along the X-axis direction, and the second fluid (colored portion in the figure) flows in the X-axis direction by flowing through the groove portion. The flow passage 21 is installed vertically below the ejection head 11, and is positioned so that the first fluid droplets ejected from the ejection head 11 land on the liquid surface of the second fluid flowing through the flow passage 21. It is adjusted (see FIG. 2). The shape of the flow passage 21 is arbitrary, and for example, the middle of the flow path of the flow passage 21 may be curved, or the cross-sectional shape of the flow path may be changed. However, in order to keep the flow condition (flow velocity) of the second fluid constant, it is desirable to have a portion in which the flow path is in a linear direction. In the present embodiment, a gel-like gel is generated by combining gels (droplets of the first fluid) with each other in the flowing second fluid. Therefore, it is because it becomes easy to produce | generate a highly accurate filamentous gel by making flow conditions constant. Moreover, since the filamentous gel produced | generated when the 2nd fluid flows linearly also flows linearly, it becomes difficult to entangle a thread | yarn and it becomes easy to produce | generate a long filamentous gel.

  The second fluid tank 22 is a container that stores the second fluid, and continuously supplies the second fluid to the flow passage 21 to generate the flow of the second fluid.

  The flow mechanism 23 is a flowing water generator that adjusts the amount of the second fluid that flows per unit time while flowing the second fluid, and a commercially available flowing water pump or the like can be used. However, the flow mechanism 23 is not necessarily provided as long as the second fluid can flow at a predetermined speed without using the flow mechanism 23. For example, when the second fluid is supplied to the flow passage 21 by a certain amount by the water head pressure of the second fluid tank 22 or the flow passage 21 is arranged to be inclined in the Z-axis direction, the flow mechanism Even if 23 is not provided, it is possible to cause the second fluid to flow.

(Control unit 50)
The control unit 50 generates a drive signal that is a voltage waveform signal for driving the ejection head 11 and applies it to the piezo element PZT, thereby controlling the ejection head 11 to control ejection of the first fluid. To do. In addition, when the flow unit 20 includes the flow mechanism 23, the flow rate of the second fluid may be controlled by controlling the flow mechanism 23.

<About gel generation operation>
The production | generation operation | movement of the filamentous gel in 1st Embodiment is demonstrated. In FIG. 4, the figure explaining the outline | summary of gel production | generation operation | movement is shown. In FIGS. 4A to 4D, the process in which the filamentous gel is generated is shown in chronological order.

  First, with respect to a second fluid that flows at a velocity (flow velocity) v in a predetermined direction (X-axis direction in the figure) along the fluid portion 20, the first fluid ejecting portion 10 that is fixed vertically above the first fluid The fluid is intermittently ejected by a predetermined amount (see (a) figure). In the figure, spherical droplets having a diameter d are formed by one injection. In other words, the size of the diameter d of the formed droplet can be adjusted by changing the amount of the first fluid ejected from the fluid ejecting unit 10.

  The fluid ejecting unit 10 ejects the first fluid intermittently at the frequency f. In other words, the period from when the first droplet is ejected to when the next droplet (second droplet) is ejected is represented by 1 / f. The ejection frequency f can be adjusted by changing the waveform of the drive signal (voltage waveform signal) generated by the control unit 50.

  The droplet formed by the first fluid (the first droplet in the figure) moves in the ejection direction (Z-axis direction in the figure) and lands on the liquid surface of the second fluid ((b) (See figure). Then, by contacting with the second fluid, a chemical reaction occurs on the contact surface (shaded portion in the figure), and gelation gradually proceeds from the surface of the droplet (first fluid) to the inside. Details of this chemical reaction (gelation reaction) will be described later.

  In addition, the ejection unit 10 continues to eject the first fluid intermittently at the frequency f, and the third droplet is ejected in FIG.

  (B) After a predetermined time t has elapsed from the state shown in the figure, the first droplet is caused to flow through the second fluid and moves in the flow direction by vt (see FIG. (C)). At this timing, the second droplet (first fluid) lands on the liquid surface of the second fluid. A part of the second droplet comes into contact with a part of the first droplet. The second droplet is brought into gelation by contacting with the second fluid, and part of the second droplet is gelled in contact with the first droplet. As a result, a gel in which two spherical droplets are coupled in series as shown in FIG. A fourth droplet is ejected from the ejection unit 10.

Similarly, after a predetermined time t has elapsed from the state of (c), the gel in which the first droplet and the second droplet are combined is caused to flow into the second fluid and vt in the flow direction. (See (d) figure). At this timing, the third droplet lands on the liquid surface of the second fluid and gels while contacting a part of the second droplet. As a result, a gel is generated in which three spherical droplets are connected in series as shown in FIG. Further, the fifth droplet is ejected from the ejection unit 10.
By repeating this operation, a filamentous gel in which spherical droplets are connected in series is generated.

  Next, conditions for forming a thread-like gel will be described. FIG. 5 is a diagram for explaining the relationship between the interval P between adjacent droplets and the diameter d of the droplets.

  In this embodiment, if the frequency f when the first fluid is ejected from the fluid ejecting unit 10 and the flow velocity v of the second fluid are both constant, the interval P between adjacent droplets is P. = V / f FIG. 5A shows the case where the interval P is larger than the diameter d of the droplet (when P> d). In this case, since the adjacent droplets do not come into contact with each other, the droplets form a single spherical gel and cannot form a thread-like gel.

  On the other hand, FIG. 5B shows the case where the interval P between adjacent droplets is equal to the diameter d of the droplets (P = d). In this case, since the adjacent droplets are in contact with each other, a filamentous gel is generated as shown in the figure.

  FIG. 5C shows a case where the interval P between adjacent droplets is smaller than the diameter d of the droplets (when P <d). In this case as well, the adjacent droplets and the droplets are in contact with each other. A filamentous gel is produced. Furthermore, since the contact part (part shown with the oblique line of a figure) of droplets becomes large, the coupling | bonding of droplets becomes stronger and it can produce | generate a strong thread-like gel. However, a problem arises when the interval P between adjacent droplets becomes narrow. For example, when the interval P is smaller than the radius of the droplet (P <d / 2), the contact portion between the droplet and the droplet is too large, and the droplets become a dumpling lump. Therefore, it becomes difficult to produce a thread-like gel.

  From these, the following can be said. That is, in this embodiment, a thread-like gel can be formed under the condition of P = v / f ≦ d. Accordingly, the control unit 50 satisfies the relationship of v / f ≦ d, the first fluid ejection frequency f, the second fluid flow velocity v, and the first fluid ejection amount (the liquid to be formed). The drop diameter d) is controlled. Furthermore, it is more desirable to adjust the values of v, f, and d so that d / 2 <P ≦ d.

<About gel forming material>
The first fluid and the second fluid, which are materials that generate the gel, will be described.

(About the first fluid)
In the present embodiment, the first fluid contains polysaccharides or proteins (for example, sodium alginate, calcium alginate, potassium alginate, ammonium alginate, ethyl cellulose, methyl cellulose, pectin, gellan gum, chitosan, collagen, fibrinogen, etc.). Substance (aqueous solution) is used. Alginates are almost harmless to the human body, and their range of applicability in the medical field and the like is widened by using them as gel materials.

  The first fluid may contain an active ingredient (for example, hydroquinone, ceramide, bovine serum albumin, γ-globulin, lipiodol, bifidobacteria, vitamins, hyaluronic acid, IPS cells, etc.).

  In the present embodiment, since the first fluid droplets ejected as described above directly form a gel (capsule), the yield of the material is very high. Therefore, when a very expensive substance has to be used as a material (for example, when a fibrous gel that can be used as a biological tissue is generated, a gel is generated using a medical material as a raw material), etc. Is very effective. In addition, since the amount of fluid used can be optimized, the amount of fluid discarded is small and effective from the viewpoint of environmental protection.

(About the second fluid)
In the present embodiment, the second fluid includes a polyvalent metal salt having a gelation-inducing factor (for example, calcium salts such as calcium chloride, calcium acetate, calcium nitrate, calcium citrate, calcium lactate, and calcium carbonate). Aluminum salts such as aluminum chloride, aluminum nitrate, aluminum sulfate, aluminum acetate, aluminum phosphate, manganese salts such as manganese chloride, manganese nitrate, manganese acetate, manganese sulfate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium sulfate And the like (magnesium salts, iron salts such as ferrous phosphate, ferric phosphate, etc.) (aqueous solutions) are used.

  In the present embodiment, the first fluid comes into contact with the second fluid to cause a chemical reaction such as a crosslinking reaction, a polymerization reaction, or a polymer reaction, so that the first fluid is cured (gelled) from the surface portion of the droplet. ) Here, “curing (gelation)” includes a state in which the viscosity increases.

  Next, a chemical reaction that occurs when a sodium alginate aqueous solution is used as the first fluid and a calcium chloride aqueous solution is used as the second fluid will be described. FIG. 6 is an explanatory diagram of sodium alginate. FIG. 7 is an explanatory diagram showing an intermediate state of changing from sodium alginate to calcium alginate gel. FIG. 8 is an explanatory diagram of a calcium alginate gel.

As shown in FIG. 6, sodium alginate (C ₆ H ₇ O ₆ Na) has monovalent sodium ions bound to alginic acid. When this sodium alginate comes into contact with an aqueous solution of calcium chloride (CaCl ₂ ), divalent calcium ions (Ca ²⁺ ) are replaced with sodium ions (Na ⁺ ) of sodium alginate, so that gelation proceeds (FIG. 7). At this time, the sodium ion (Na ⁺ ) is monovalent and the calcium ion (Ca ²⁺ ) is divalent, and therefore one calcium ion (Ca ²⁺ ) with respect to two sodium ions (Na ⁺ ). Is replaced. At this time, in the sodium alginate, two sodium ions (Na ⁺ ) are eliminated between the two sodium alginate and are replaced with one calcium ion (Ca ²⁺ ) which is a divalent metal ion (FIG. 8). . Then, cross-linking condensation that bridges the two alginic acids occurs and gels (hardens). Such a chemical reaction is also called a crosslinking reaction.

  Incidentally, FIG. 8 shows a region surrounded by a broken line. In the calcium alginate gel, water molecules move from the inside of the gel to the outside through the region surrounded by the broken line, or the water molecules move from the outside to the inside. Thus, the elastic gel is realized by the presence of water molecules in the region surrounded by the broken line. The inflow and outflow of water molecules in the gel are balanced. In the present embodiment, by forming a hydrophilic gel, it is possible to generate a gel having high biocompatibility when used as a biological tissue. Moreover, since it is a hydrophilic gel, there also exists an advantage that adjustment of the osmotic pressure through a gel becomes easy between the said gel and external environment.

<Effects of First Embodiment>
In the first embodiment, droplets are formed by ejecting the first fluid intermittently with respect to the second fluid that continuously flows in a predetermined direction like a river. Then, while the first droplet flows in the second fluid, the second droplet is brought into contact with the first droplet to generate a gel in which the two droplets are combined. By repeating this operation, a filamentous gel in which a plurality of droplets (gels) are connected in series can be generated.

  Moreover, since the produced | generated filamentous gel can be made hard to get entangled by flowing the 2nd fluid linearly, it becomes easy to produce | generate the filamentous gel of desired length.

<Modification>
In FIG. 2, the configuration in which the fluid ejecting unit 10 (ejection head 11) of the gel manufacturing apparatus 1 has one nozzle is described, but the liquid ejecting unit 10 may have a plurality of nozzles. In FIG. 9, the schematic of the gel manufacturing apparatus 1 in a modification is shown.

  The fluid ejecting unit 10 according to the modified example includes a plurality of nozzles arranged in a direction intersecting the flow direction of the second fluid. In the case of FIG. 9, the first fluid is ejected from a plurality of nozzles arranged in the Y-axis direction with respect to the second fluid flowing in the X-axis direction. Since a plurality of droplets (first fluid) can be ejected at the same timing, a plurality of filamentous gels are generated at the same time, and the filamentous gel can be generated more efficiently. In addition, if the flow path 21 of the flow part 20 is linear, the flow of the second fluid is likely to be a laminar flow, so that the plurality of filamentous gels can be prevented from being entangled with each other.

=== Second Embodiment ===
In 2nd Embodiment, a filamentous gel is produced | generated using the gel manufacturing apparatus 2 which injects a 1st fluid with respect to the 2nd fluid which flows in a spiral shape.

<Configuration of gel production apparatus>
FIG. 10 is a schematic view of the gel manufacturing apparatus 2. In the gel manufacturing apparatus 2, the configuration of the fluidizing section 20 is different from that of the gel manufacturing apparatus 1. The configurations of the fluid ejecting unit 10 and the control unit 50 are the same as those of the gel manufacturing apparatus 1.

(Fluid part 20)
The flow section 20 of the gel manufacturing apparatus 2 includes a flow container 25 and a stirrer 26.
As shown in FIG. 10, the flow container 25 is a cylindrical container having an upper opening, and stores the second fluid in a liquid state therein. Therefore, the fluid container 25 is formed of a material such as glass that does not cause a chemical reaction even when it comes into contact with the second fluid. Further, the fluid container 25 is installed vertically below the fluid ejecting unit 10 so that the first fluid ejected from the fluid ejecting unit 10 lands in the second fluid stored in the fluid container 25. The position is adjusted. Details of the installation position adjustment will be described later.

  The stirrer 26 includes a power unit 261 and a rotor 262. The power unit 261 is provided below the flow container 25, and rotates the rotor 262 on a plane parallel to the XY plane by a magnetic force. At that time, it is possible to adjust the rotation speed and rotation direction of the rotor 262.

  The rotor 262 is an elongated rod-like member and is provided inside the flow container 25. The second fluid (liquid) stored inside the fluid container 25 is swirled by being rotated by the power unit 261. Here, the rotation center of the rotor 262 is adjusted so as to coincide with the center position of the flow container 25, and the second fluid flows in a vortex around the central axis of the flow container 25.

<About gel generation operation>
In the second embodiment, the same material as the first embodiment can be used for the first fluid and the second fluid.

  The generation operation of the filamentous gel in the second embodiment is basically the same as that of the first embodiment. However, in the present embodiment, the second fluid rotates and flows in a spiral shape. That is, the flow velocity v of the second fluid is represented by the velocity in the rotation direction of the second fluid at a position facing the nozzle 111 of the fluid ejecting unit 10. In FIG. 10, the first fluid is ejected from the fluid ejecting unit 10 vertically downward (Z-axis direction). Therefore, when the first fluid lands at a position r away from the center of rotation of the second fluid, the velocity in the tangential direction of the circumference of the radius r from the center of the flow container 25 has a flow rate of the second fluid. The speed becomes v (see FIG. 10).

  Since the conditions of the ejection cycle (1 / f) of the first fluid and the diameter (d) of the formed droplet are the same as those in the first embodiment, d ≧ v / f (= P) is satisfied. By controlling each value, a gel (thread-like gel) in which spherical gels are connected in series can be generated.

  In this embodiment, it is difficult to measure the flow velocity v of the second fluid that is actually rotating and flowing. Therefore, the optimum flow velocity v is experimentally adjusted. Specifically, the condition (rotation condition) when the gel is generated while changing the rotation speed of the stirrer 26 in a state where the frequency f and the diameter d of the droplet are constant is obtained and the gel is connected in a string form is obtained. It is done.

  In the present embodiment, since the second fluid is swirled and swirled using the stirrer 26, there may be a portion where the liquid level of the second fluid is not flat. For example, in the vicinity of the center of rotation (the center of the fluid container 25), the liquid level of the second fluid has a mortar-like shape (funnel shape), and the liquid level is likely to be distorted. If the first fluid is ejected to a portion where the liquid surface is distorted (a portion that does not become horizontal), there is a possibility that a highly accurate thread-like gel cannot be generated. Therefore, in the present embodiment, the liquid ejecting unit 10 and the flow unit 20 (flow container 25) are arranged such that the liquid droplet of the first fluid lands on a portion where the liquid level of the second fluid that rotates and flows is substantially horizontal. ) Is adjusted.

<Effects of Second Embodiment>
In the second embodiment, a filamentous gel is generated while the second fluid is swirled. In the first embodiment, since the second fluid is made to flow linearly, it is necessary to continuously flow a large amount of fluid. On the other hand, in this embodiment, if there is an amount of the second fluid stored in the flow container 25 of the flow section 20, a gel can be generated. That is, the amount of the second fluid used can be saved, and the manufacturing cost of the gel can be reduced.

  Moreover, since the installation area of the flow part 20 is small compared with 1st Embodiment, the structure of a gel manufacturing apparatus becomes compact and can attain space saving.

=== Third Embodiment ===
In the third embodiment, the filamentous gel is generated while changing the amount of the first fluid ejected from the fluid ejecting unit 10. By changing the ejection amount of the first fluid, the diameter d of the formed droplet is also changed. That is, a string-like gel having a non-uniform thickness can be generated by connecting droplets having different sizes in series. The gel manufacturing apparatus used in the third embodiment is the same as the gel manufacturing apparatus 1 or 2 described above.

  In FIG. 11, the example of the filamentous gel produced | generated by 3rd Embodiment is shown. In the third embodiment, a filamentous gel whose thickness changes midway as shown in the figure is generated. For example, in the case of FIG. 11A, a filamentous gel is formed by droplets having a diameter d until halfway, and a filamentous gel is formed by droplets having a diameter of 1.5d from the middle. That is, a filamentous gel whose thickness changes 1.5 times from the middle can be generated.

  In the case of FIG. 11B, among the plurality of droplets forming the filamentous gel, the diameter of a part of the gel is 2d and the diameters of the other gels are d. For example, when a filamentous gel is used as a biological tissue, there is a case where it is desired to encapsulate a cell tissue inside a part of the gel. In such a case, the gel encapsulating the cell tissue needs to have a predetermined size or more. This is because if the gel serving as the enclosure is too small, the cell tissue may be killed. Accordingly, there may be a need to produce a filamentous gel that partially includes a large gel as shown in FIG.

  In the present embodiment, a droplet having a desired size (diameter d) can be generated by changing the amount of the first fluid ejected from the fluid ejecting unit 10. The ejection amount of the first fluid is adjusted by changing the waveform of the drive signal applied to the piezo element PZT of the ejection head 11.

  In order to generate a filamentous gel, it is necessary to satisfy d ≧ v / f (= P) as described above, but it is difficult to adjust the flow velocity v of the second fluid. Therefore, the condition of d ≧ v / f is satisfied by adjusting the ejection frequency f of the first fluid according to the magnitude of d. The frequency f can also be adjusted by changing the waveform of the drive signal applied to the piezo element PZT.

<Effect of the third embodiment>
In the third embodiment, a gel (thread-like gel) in which gels having different sizes (diameters) are connected in series is generated by changing the injection amount of the first fluid and the frequency at the time of injection. The Thereby, the filamentous gel from which thickness differs partially can be produced | generated.

=== Fourth Embodiment ===
In each of the above-described embodiments, the first fluid and the second fluid are brought into contact with each other to cause a chemical reaction, whereby the first fluid is gelled. In contrast, in the fourth embodiment, the first fluid is gelled by cooling. The manufacturing apparatus used in the fourth embodiment is the same as the gel manufacturing apparatus 1 or 2 described above.

  In the present embodiment, a material such as gelatin or agar that is in a liquid state at normal temperature (or at a high temperature) but gels and hardens (gels) when cooled is used as the first fluid. A liquid that cools the first fluid is used as the second fluid. For example, cold water can be used. As long as the second fluid does not chemically react with the first fluid and can cool the first fluid, a substance other than water can be used. However, by using water, The cost can be kept low and the fluid can be easily handled.

  When the gel is produced, the gel production apparatus 1 or 2 is used to bring droplets of the first fluid (eg, gelatin) ejected intermittently into contact with the second fluid (eg, cooling water). The gelatin is cooled and gelled. Thereby, a thread-like gel can be produced | generated. At that time, it is possible to adjust the hardness of the gel by changing the temperature of the second fluid used for cooling. In the present embodiment, the first fluid is cooled by maintaining the second fluid at a predetermined temperature of 10 ° C. or lower. In order to stably gelatinize the gelatin, the temperature range of the second fluid is desirably about 2 ° C. to 6 ° C. Therefore, you may provide the cooling device (not shown) for adjusting the temperature of the flow part 20. FIG. However, if the first fluid can be gelled, the temperature of the second fluid can be higher than 10 ° C. Further, the hardness of the gel can be adjusted by changing the gelatin concentration.

  In this embodiment, by forming a filamentous gel using gelatin whose main component is collagen, it can be easily applied to cosmetics using a moisturizing component of collagen in addition to the above-mentioned application in the medical field. Become.

<Effects of Fourth Embodiment>
In 4th Embodiment, a filamentous gel is produced | generated using the liquid which gelatinizes by cooling. Since water can be used as the second fluid, the material cost is low, and it is easy to obtain and handle. Moreover, since the hardness of a gel can be easily adjusted with temperature, the filamentous gel of desired hardness can be produced | generated according to a use.

=== Fifth Embodiment ===
In the fifth embodiment, the first fluid is gelled by an enzymatic reaction. The manufacturing apparatus used in the fifth embodiment is the same as the gel manufacturing apparatus 1 or 2 described above.

  In the present embodiment, the first fluid is a liquid such as fibrinogen, but a substance that gels and hardens by an enzymatic reaction is used. A solution containing an enzyme is used as the second fluid.

  When the gel is produced, the gel production apparatus 1 or 2 is used to bring droplets of the first fluid (for example, fibrinogen aqueous solution) intermittently ejected into contact with the second fluid (enzyme solution). Fibrinogen is gelled by enzymatic reaction. Thereby, a thread-like gel can be produced | generated. At that time, the hardness of the gel can be adjusted by changing the enzyme concentration of the second fluid used in the reaction. The gel hardness can also be adjusted by changing the fibrinogen concentration.

  In this embodiment, by producing a filamentous gel using an aqueous fibrinogen solution, it can be easily applied to the biotechnology field such as cell culture in addition to the medical field application as described above.

<Effect of Fifth Embodiment>
In the fifth embodiment, a filamentous gel is generated using a liquid that gels by an enzymatic reaction. Since the hardness of the gel can be easily adjusted by changing the concentration of the first fluid or the second fluid, a filamentous gel having a desired hardness can be generated according to the application. In addition, it can be applied to various fields.

=== Other Embodiments ===
Although the gel manufacturing apparatus as one embodiment has been described, the above embodiment is for facilitating the understanding of the present invention, and is not intended to limit the present invention. The present invention can be changed and improved without departing from the gist thereof, and it is needless to say that the present invention includes equivalents thereof. Even the embodiments described below are included in the present invention.

<About gel forming material>
In each of the above-described embodiments, specific examples are illustrated for the first fluid and the second fluid, respectively, but it is also possible to generate a filamentous gel using a gel generating material other than those illustrated.

<Applications of filamentous gel>
In each of the above-described embodiments, the use of the filamentous gel has been described as a medical material such as a surgical thread or living tissue. However, the filamentous gel is used for a wide range of uses other than those exemplified. be able to. For example, the use as cosmetics, the use as functional food, etc. can be considered.

<About the fluid ejection unit 10>
In each of the above-described embodiments, the piezoelectric element (piezo element PZT) is used as the liquid ejecting unit that ejects the droplet of the first fluid. However, the liquid ejecting unit may use another mechanism. . For example, various mechanisms such as a mechanism using a dispenser that drops liquid by pushing a syringe, a liquid ejecting mechanism using an electrostatic actuator, a liquid ejecting mechanism using an electrostatic suction method, a liquid ejecting mechanism using acoustic energy, etc. A mechanism can be used. At this time, it is desirable that the mechanism be capable of arbitrarily changing the amount of the first fluid to be ejected and the ejection cycle.

1, 2, gel production equipment,
10 liquid ejecting section, 11 ejecting head, 12 first fluid tank,
20 fluid part, 21 fluid passage, 22 second fluid tank, 23 fluid mechanism,
25 Fluid container, 26 Stirrer 26, 261 Power unit, 262 Rotor,
50 Control unit

Claims (9)

A fluid ejection unit that ejects the first fluid;
A fluidizing section for causing the second fluid to flow in a predetermined direction;
A control unit for controlling the operation of the fluid ejection unit;
A gel manufacturing apparatus comprising:
The controller is
Injecting the first fluid into the flowing second fluid to produce a first gel;
Injecting the first fluid into the flowing second fluid to contact a portion of the first gel in the second fluid to produce a second gel;
The gel manufacturing apparatus, wherein the first gel and the second gel are generated in a state of being connected in series. The gel manufacturing apparatus according to claim 1,
The frequency at which the first fluid is intermittently ejected from the fluid ejecting unit is f, the diameter of the gel formed by the first fluid is d, and the flow velocity of the second fluid is v. When
v / f ≦ d
The gel manufacturing apparatus characterized by satisfying the relationship. The gel manufacturing apparatus according to claim 1 or 2,
The said flow part is made to flow so that the flow direction of a said 2nd fluid may have a part used as a linear direction, The gel manufacturing apparatus characterized by the above-mentioned. The gel manufacturing apparatus according to claim 1 or 2,
The said flow part rotates the said 2nd fluid in the shape of a vortex, The gel manufacturing apparatus characterized by the above-mentioned. It is a gel manufacturing apparatus in any one of Claims 1-4,
The first fluid is an aqueous solution containing polysaccharides or proteins;
The second fluid is an aqueous solution containing a polyvalent metal salt;
A gel producing apparatus, wherein the first fluid is brought into contact with the second fluid to produce a gel by a curing reaction. It is a gel manufacturing apparatus in any one of Claims 1-4,
The first fluid is a liquid that gels when cooled,
The second fluid is a liquid that cools the first fluid;
A gel producing apparatus, wherein the first fluid is brought into contact with the second fluid and cooled to produce a gel. It is a gel manufacturing apparatus in any one of Claims 1-4,
The first fluid is a liquid that gels by an enzymatic reaction,
The second fluid is an aqueous solution containing an enzyme,
A gel producing apparatus, wherein the first fluid is brought into contact with the second fluid to produce a gel by an enzymatic reaction.   The medical gel manufactured with the gel manufacturing apparatus in any one of Claims 1-7. Injecting a first fluid onto a second fluid flowing in a predetermined direction to produce a first gel;
Injecting the first fluid into the flowing second fluid to produce a second gel so as to contact a portion of the first gel in the second fluid;
A gel production method of producing a gel in a state where the first gel and the second gel are connected in series.